Quaternary quinoline carboxamide salts and method of preparing same



United States Patent i QUATERNARY QUINOLINE 'CARBDXAMIDE SALTS AND METHOD OF PREPARING SAME Cornelius K. Cain, Flourtown, Pa, assignor to McNeil Laboratories, Inc., Philadelphia, Pa'., a corporation of Pennsylvania NoDrawing. Application February 4, 1954, Serial N0. 408,280

IZ-Claiins. romeo-286 The present invention relates-to novel'chemical compounds and to the method of preparing the same; and,

'more particularly the invention relates to qua-ternary quinoline carboxamide salts possessing valuable hypotensive'properties for use in the therapy and relief of hypertension.

Many agents are known to produce-a lowering of blood pressure in a living body. Unfortunately, these substances possess such limitations and disadvantages as to render them practically unusable as specific therapeutic agents'in the treatment and relief of hypertension. Thus,

in many cases the hypotensive effect of these agents is sirable effects'on the system.

Another object of the invention is to provide new chemical compounds having the described" properties which may be administered orally as well as parenterally.

Further objects including the provision of a method of making the novel compounds will become apparent from a consideration of the following specification and claims.

The novel compounds of the present invention are quaternary quinoline carboxamide salts comprising the fundamental structural formula:

(%NH'R1 X- R whereR is selected from the group consisting of aliphatic groups containing from 1 to 4 carbon atoms, benzyl, methoxy benzyl, ethoxy benzyl, methyl'benzyl and methoxy methyl benzyl groups; Where R1 is selected from the group consisting of alkyl groups containing from 1 to 3 carbon atoms and an AY group Where A-is selected from the group consisting of alkylene groups containing froml to carbon atoms; mercaptoalkylene group's,' 'the alkylene group of which contains from 1 to 3 carbon atoms; methylmercaptoalkylene groups, the alkylene group of which contains from 1 to 3 carbon atoms; carboxyalkylene groups, the alkylene group of which contains from 2 to 3 carbon atoms; carbethoxyalkylene groups, the alkylene group of which contains from 2 to 3 carbon atoms; a phenylene' group; and a phenyl alkylene group, the alkylene group of which contains from 1 to 3 carbon atoms; and where Y is selected from the group consisting of --CN, COOH, CONH2, and COORz,

R2 being an alkyl group containing from 1 to 4 carbon atoms; and Where X denotes an acid anion.

.ofsuch isomers.

a amino-B-methylmercaptopropionic acid,

2,798,076 Patented July 2, 1957 ice '2 In the compounds, the

-("3NH-R1 group may belocated, in accordance with the broader aspects of the invention, at the 2, 3 or 4 position, and the productmay actually comprise -a mixture of two or more In-the preferred compounds, however, the

group is located at the 3 position.

As stated, R may be an aliphatic group containing from 1 to 4 carbon atoms, that is methyl, ethyl, n-propyl,

isor-propyl, allyl,:n-butyl, sec-butyl or tert-butyl. -R may alsobe a benzyl group, .a.methoxy-substituted benzyl -gro1ip,-anethoxy-substituted benzyl group, a methylsubstituted'benzyl group or a methoxy methyl-substituted benzyl group.

-NH--R1'is a secondary amine group bonded to the remainder of the compound through the aminonitrogen.

-R1 maybe a-simple alkyl group containing. from 1 to 3 .carbon atoms, such as methyl, ethyl, n-propyl or isopropyl. -NHR1 may also be provided by an amino acid, preferably a naturally occurring monoamino acid,

or'a derivative thereof. The naturally occurring monoamino acids represent a limited well known group of compounds including glycine, alanine, beta alanine, valine, leucine, isoleucine, phenylalanine, paramino benzoic acid, tyrosine, 'serine, threonine, cysteine, homocysteine, methionine, aspartic acid, glutamic acid, proline and hydroxyproline. Other amino acids not found in 'nature, or derivatives thereof, may provide NHR1,

such as amino malonic acid, u-amino pimelic acid,

a-amino-amethylmercaptovaleric acid, a-amino-'y-methylmercaptoisovaleric acid, rx-amino-e-methylmercaptoadipic acid,

and the like.

NHR may be the acid itself or it may be an alkyl ester thereof wherein the alkyl group contains froml to 4 carbon atoms, such as those alkyl groups mentioned above in connection'with 'R, the amide thereof or the nitrile corresponding thereto.

' Reference is made above to naturally occurring acids to designate those which are formed in nature. However,

it willberealized that, in practice, the particular naturally occurring amino acid or derivative thereof providing -NI-IR1 maybe synthesized. Of the amino acids, the'alpha monamino acids which can be derived fromproteins are preferred for use in preparing the compounds of the invention.

X is an acid radical to provide the quaternary salt, and

may be derived from any desired inorganic or organic acid, for example, hydrochloric, hydrobromic, hydroiodic, nitric, sulphuric, phosphoric, and the like; acetic, propionic, *caproic, stearic, and other acids ofthis series, and the like; crotonic, oleic, oxalic, citric,.tartaric, lactic, benzoic, naphthoic, picric, salycylic, dilituric, 'methylsulphuric, methane sulpho'nic, camphor sulphonic, and the like. If the salt is to be administered, any toxicity which'may be imparted by the acid should be taken into consideration as well known in the art. The halogen salts, particularly the iodides, have been found to be particularly advantageous. I

The compounds of the invention possess valuable hypotensive properties. Tests have shown that their mosti-m portant site of action'in producing a fall of blood pressure is peripheral; a central componentalso contributes to this effect. The compounds in. generalpossess a wide margin of safety,-that is to say, the level required to provide significant relief from hypertension is well below atoms and in which R1 is, in the foregoing formula,

AY, where A is an alkylene or phenylene group and Y is COOR2 as defined above. In this connection, the compounds in which NH-R1 is provided by the methyl or ethyl ester of alanine (NE -(EH O OH) CH3 or of glycine (NHzCHzCOOH) are particularly advantageous, especially when R is methyl.

The compounds are readily prepared by reacting one mol of quinoline carboxylic acid, acid halide (preferably the chloride) or an addition salt thereof (preferably the hydrochloride) with one mol of the appropriate amino compound providing NHR1. Where, in the ultimate product, -NHR1 is to be the monaminoacid group itself an ester derivative may first be produced following which the ester may be hydrolyzed to form the corresponding acid. Likewise, the nitrile derivative may first be produced following which it may be converted to the desired ester.

When an amino acid or derivative is one of the reactants, the reaction may be carried out in an aqueous solution of sodium carbonate. The resulting mixture can then be extracted with, for example, ether or chloroform, and the product recovered from the ether or chloroform layer. When R1 is to be a simple alkyl group the appropriate primary amine may be reacted with quinoline carboxylic acid halide or addition salt; or a salt of the amine, for example, an alkyl amine hydrochloride, may be reacted with the quinoline carboxylic acid. In either event the reaction may take place in phosphorus oxychloride. Following the reaction, the mixture is neutralized with, for example, sodium hydroxide and extracted with .an organic solvent, such as ether, the product being recovered from this solvent,

The temperature employed during the reaction will depend primarily upon the product to be produced. Thus, where NH-R1 is to contain an ester group it .is desirable to operate at relatively low temperatures, such as from 0 to 30 C.; whereas when R1 is to be an alkyl group only it is preferred to employ higher temperatures which may go up to about 110 C., as in an oil bath.

The resulting quinoline carboxamide compound is then converted to the desired quaternary salt by reaction with one mol of a compound, RX, in which R provides the desired R group and X the desired acid radical in the generic formula set forth above. Generally this quaternization reaction can be conducted at an elevated temperature as by refluxing the reactants in, for example, benzene until the product precipitates. The product may then be separated from the reaction medium, as by filtration, and recrystallized from, for example, methanol, a mixture of methanol and ether, or the like.

The following examples serve to illustrate further the products of the present invention and their preparation:

Example I To 8.0 g. of finely powdered 3-quinoline carboxylic acid and 3.7 g. of ethylamine hydrochloride are added 4.5 g. of phosphorus oxychloride. The mixture is heated in an oil bath at 110 C. for 12 hours, and then allowed to cool. The solid mass is decomposed with 30% aqueous sodium hydroxide and extracted with chloroform. Removal of the solvent and recrystallization of the residue from benzene gives 6.5 g. of N-ethyl-3-quinoline carboxamide, melting at 130-132 C.

A mixture of 6.5 g. of this N-ethyl-3-quinoline car- 4 boxamide, 15 m1. of methyl iodide and ml. of benzene is refluxed for 12 hours. The product obtained is recrystallized from a mixture of methanol and ether to give 1-methyl-3-(N-ethylcarbamyl) quinolinium iodide, melting at 212-215 C. The calculated N content for CisHislNzo is 8.2; that found is 8.0.

A little over 32 mg. of this compound per kilogram of body weight lowers the mean blood pressure substantially for 20 minutes.

Example II Following the procedure of Example I but employing ethyl iodide in place of methyl iodide, 1-ethyl-3-(N-ethylcarbamyl) quinolinium iodide is obtained. The product melts at 200202 C. The calculated N content for C14H21IN2O is 7.8; that found is 7.6.

A little over 31 mg. of this compound per kilogram of body weight lowers the mean blood pressure substantially for 20 minutes.

Example III A solution of 6 g. of crude 3-quinolinecarbonyl chloride in 50 ml. of chloroform is added gradually to a wellstirred and cold mixture of 3.7 of ethyl alaninate, 3.3 g. of sodium carbonate and 25 ml. of water. The mixture is shaken intermittently over a period of three hours and then allowed to stand overnight in a refrigerator. A small amount of inorganic material is removed by filtration, and the chloroform layer is separated and dried over anhydrous sodium sulfate. The chloroform is removed under vacuum, and the solid product washed with heptane and dried. Ethel N-(3-quinolinecarbonyl) alaninate is produced which is recrystallized from a benzeneheptane mixture.

A mixture of 3.1 g. of this compound, methyl iodide and dry benzene is refluxed for two hours. The solid product is filtered ofiE and recrystallized from a methanol-ether mixture. The product, 1-methyl-3[N-(l-carboethoxyethy1)- carbamyl] quinolinium iodide, melts at 185-186 C. The calculated N content for C16H19IN203 is 6.8; that found is 6.4.

Only 25-16 mg. of this compound/kilogram of body weight reduces the mean blood pressure substantially for 20 minutes.

Example IV Following the procedure of Example III but using methyl bromide in place of methyl iodide provides lmethyl-3 [N- l-carboethoxyethyl) carbamyl] quinolinium bromide melting at 181-1825 C. The calculated N content for C1sH19BrN2O3 is 7.6; that found is 7.7.

By following the same procedure but using, in place of ethyl alaninate, propyl alaninate, isopropyl alaninate, butyl alaninate or sec-butyl alaninate, the corresponding l-methyl 3 [N-(l-carbopropoxyethyl)canbamyl] quinolinium iodide, 1-methyl-3- [N- l-carboisopropoxyethyl)- carbamyl] quinolinium iodide, 1-methyl-3-[N-(l-carbobutoxyethyl)carbamyl] quinolinium iodide and l-methyl-3- [N (1 -carbosecondarybutoxyethyl)carbamyl] quinolinium iodide, may be prepared.

Likewise, by using ethyl cystinate or ethyl homocystinate in place of the ethyl 'alaninate and reducing the disulfide derivatives thereof by conventional methods, the corresponding 1 methyl-3-[N-(l-earbethoxy-Z-mercaptoethyl)carbamyl] quinolinium iodide and 1-..1ethyl-3-[N- (1 carbethoxy-3-mercaptopropyl)carbamyl] quinolinium iodide, respectively, may be prepared.

Example V Following the same procedure as in Example III but using ethyl iodide instead of methyl iodide, 7.5 g. of 1- ethyl-3-[N-(l-carboethoxyethylcarbamyl)] quinolinium iodide are produced from 6.2 g. of ethyl N-(3-quinolinecarbonyl) alaninate. The product melts at -157" C. The calculated N content for C17H21'I-N2O3 is 6.5; that found is 6.2.

Slightly over 32 mg. of this compound/kilogram of body'weight reduces the mean blood pressure substantially for 20 minutes.

The corresponding 1-propyl 3- [N-( 1-carbethoxyethyl)- carbamyl] quinolinium iodide, 1-isopropyl-3-[N-(l-carbethoxyethyl)carbamyl] quinolinium iodide, 1 buty1-3- [N-(l-carbethoxyethyl)carbamyl] quinolinium iodide and 1-sec-butyl-3-[N-(1-'carbethoxyethylycarbamyl] quinolinium iodide may be prepared by using, in the foregoing procedure, propyl iodide," isopropyl iodide, butyl iodide or sec-butyl iodide in place of the ethyl iodide.

Example VI A solutiontof'5 g. of 3-quinolinecarbonyl chloride in 50 ml; chloroform is added slowly to a mixture of 4 g. of a-aminopropionitrile, water and sodium carbonate cooled in an ice bath. The mixture is shaken thoroughly and the aqueous layer extractedwith ether. The solvent is removedfrom the combined extracts and theresidue dried under vacuum at 50 C. After recrystallization from benzene, the resulting compound melts at 129- 130.5 C.

Gaseous hydrogen chloride is passed into a cold solution of 1.8 g. of'the resulting a-(3-quinolinecarboxamido) propionitrile in 30ml. methanol. x(3-quinolinecarboxamido) propionitrile hydrochloride immediately separates from the solution and on further addition of hydrogen chloride, the precipitated solid gradually disappears. The clear solution is allowed to stand in a refrigerator for 18 hours. At the end of this time, the white product that separates from the solution is removed by filtration, washed with dry ether, and dried in a vacuum desiccator over solid potassium hydroxide.

1.5 g. of the resulting a-(3-quinolinecarboxamido) propionimidic acid methyl ester dihydrochloride are dissolved in 10ml. of water and carefully neutralized with 5% sodium carbonate. The solid product that separates from the solution is removed by filtration and recrystallized from a water-methanol mixture.

A mixture of 0.1 g. of the resulting methyl a-(3-quinolinecarboxamido) propionate, 5 ml. of methyl iodide and ml. of dry benzene is refluxed for two hours. The product is removed by filtration and recrystallized from a methanol-ether mixture. The resulting 1-methyl-3- [N-( l-carbomethoxyethyl) carbamyl] quinolinium iodide melts at 206207 C. The calculated N content for CrsHrzINzOa is 7.0; that found is 7.2.

Example VII Following the same procedure as in Example VI but using methyl bromide in place of methyl iodide provides the corresponding l-methyl-3-[N-(l-carbomethoxyethyl)carbamyl] quinoliniurn bromide which decomposes at 194-196" C. The calculated N content for CH17BrN2O3 is 8.0; that found is 8.0.

Example VIII Following the procedure set forth in Example III but using ethyl glycinate instead of ethyl alaninate, ethyl 3-quinolinecarboxamidoacetate is prepared. By refluxing 2 g. of this product with 15 ml. of methyl iodide in dry benzene for two hours, 1-methyl-3-(N-(carboethoxymethyl)carbamyl)quinolinium iodide is obtained which, after filtration and recrystallization from a methanolether mixture, melts at 197-1985 C. The calculated N content for C15H17IN203 is 7.0; that found is 6.9.

Slightly over 32 mg. of-this compound/kilogram of body weight lowers the mean blood pressure substantially for minutes.

Example IX Ethy a-(S-quinolinecarboxamido)propionate is prepared following the procedure set forth in Example III. This ester is hydrolyzed to produce the corresponding a-(3-quinolinecarboxamido) propionic acid.

A mixture of 0.7 g. of this compound and '10 ml. of methyl iodide in' dry benzene is allowed to stand for 4 days. The solvent is then removed under vacuum and the residue recrystallized from a methanol=ether mixture. 1 methyl-3-[N- 1-carboxyethyl)carbamyl] quinolinium iodide is obtained which melts at 122-125 C. The calculated N content for C14H15IN2O3 is 7.4; that found is 7.3;

Slightly over 32 mg. of this compound per kilogram of body weight reduces? themean blood pressure substan tially for 20 minutes.

Example X A mixture of ethyl a-(3-quinolinecarboxamido)propionate, which is prepared following the procedure set forth in Example III. and 28% ammonium hydroxide solution is allowed to stand overnight at room temperature. The mixture is evaporated to dryness under vacuum and the residue recrystallized, with charcoal, several times from' water.

A mixture of'3.7 g; of the resulting a-(3-quinolinecarboxamido)propionamide, ml. of dimethyl formamide and 20 ml. of methyl. iodide is refluxed for 11 hoursand then cooled. The methiodide which separates on cooling is removed by filtration and recrystallized several times from. dimethylformamide. There is obtained l-methyl 3 [N-( l-carboxamidoethyl)carbamyl] quinoliniumiodide, melting at 239-241 C. The calculated N content for CmHislNsOa is 10.9; that found is 10.6.

Slightly over 32 mg. of this compound per kilogram of body weightlowers themean blood pressure substantially for- 20' minutes.

Example XI A. mixture of3.5'g. of 3,-quinolinecarboxylic acid and 25 ml. of thionyl chloride is refluxed for about an hour until all theacid is. dissolved. The excess thionyl chloride isremoved under vacuum and the residue suspended in chloroform. A solution of 4 g. of sodium carbonate in water is added, and the suspensiongoes into solution on shaking. To this mixture is added; with shaking, a solution of 4- g. of ethyl phenylalaninate hydrochloride in Water. The reactionmixture is then placed in a refrigerator and allowed to stand overnight. The layers are then separated, and the water layer is extracted with chloroform. The solvent is removed under vacuum, and the residue recrystallized from a benzene-heptane mixture.

A mixture of 2.6 g.,of the resulting ethyl a-(3-quinolinecarboxamido)hydrocinnamate, 100 ml. of dry benzene and 15 ml. of methyl iodide is refluxed for 16 hours. The benzene is decanted and the residue recrystallized from a methanol-ether mixture. There is obtained l-methyl-3- [N- a-carbethoxyphenethyl) carbamyl] quinolinium iodide melting at 152154.5 C. The calculated N content for CzzHzsINzOs is 5.7; that found is 5.4.

Example XII A solution of 9.7 g. of a-(S-quinolinecarboxamido) propionitrile, prepared in accordance with the procedure of Example VI, in 100 ml. of dry benzene is refluxed with. 20 ml. of methyl iodide for eight hours. The ben zeneis decanted and the residue is recrystallized from methanol. There is obtained 6 g. of l-methyl-S-[N- (l-cyanoethyl)carbamyl] quinolinium iodide melting at 171-172.5 c.

Example XIII Following the procedure of Example Xi for the preparation of ethyl a-(B-quinolinecarboxamido) hydrocinnamate, but employing g. of 3-quinolinecarboxylic' acid and 9.5 g. of ethyl p-aminobenzoate, results in ethyl p-(3-qninolinecarboxamido) benzoate.

A solution of 4 g. of this compound and 15 ml.- of

methyl iodide in dry benzeneand a small amount of dimethylformamide is refluxed for 10 hours. The solid product is filtered off, and recrystallized from a methanolwater mixture. The resulting l-methyl-S-(N-p-carbethoxyphenylcarbamyl) quinolinium iodide melts at 246 248 C. The calculated N content for C2oH19IN2O3 is 6.1; that found is 5.9.

4-8 milligrams of the compound per kilogram of body weight lowers the blood pressure substantially.

Example XIV A solution of 5 g. ethyl a-(3-quinolinecarboxamido) propionate, prepared in accordance with the procedure set forth in Example III, and 5 g. of benzyl chloride in dried benzene is refluxed for 48 hours. The solvent is removed under vacuum. The product, which precipitates as a dark oil and recrystallizes slowly on the addition of ether, is recrystallized from a methanol-ether mixture. The resulting 1-benzyl-3-[N-(l-carbethoxyethyl)carbamyll quinolinium chloride melts at 177- 179 C. The calculated N content for CzzHzaClNzOa is 7.0; that found is 6.8.

Example XV A solution of 4 g. of ethyl N-(3-quinolinecarbonyl) alaninate, prepared in accordance with the procedure set forth in Example III, and 8 g. of 2-methoxy-5-methylbenzyl chloride in 200 ml. of dry thiophene-free benzene is refluxed for 6 hours. The crystallized product is removed by filtration, and recrystallized from a mixture of methanol and ether. The resulting 3-[N-(1- carbethoxyethyl)carbamyl] 1-(2-methoxy-5-methylbenzyl) quinolinium iodide melts at 158-158.5 C. The calculated N content for C24Hz7ClN2O4 is 6.3; that found is 6.5.

3664 milligrams of the compound per kilogram of body weight lowers the blood pressure substantially.

Following the same procedure but using p-methoxybenzyl chloride, o-ethoxybenzyl chloride or p-methylbenzyl chloride in place of 2-methoxy-5-methylbenzyl chloride, the corresponding I-(p-methoxybenzyD-S-[N- (l-carbethoxyethyl)carbamyl] quinolinium chloride, 1- (o-ethoxybenzyl)-3-[N (1 carbethoxyethyl)carbamyl] quinolinium chloride and 1-(p-methylbenzyl)-3-[N-(1- carbethoxyethyl)carbamyl] quinolinium chloride, respectively, are prepared.

Example XVI Following the procedure of Example XI for the preparation of ethyl a-(3-quinolinecarboxamido)hydrocinnamate, but using 11 g. of 3-quinolinecarboxylic acid and 12 g. of leucine ethyl ester hydrochloride, results in ethyl N-(3-quinolinecarbonyl)leucinate.

A solution of 6 g. of this compound in 150 ml. of dry benzene is treated with 15 ml. methyl iodide and allowed to stand at room temperature for 72 hours. Ether is added to the mixture and the solvent decanted. The residue is crystallized from isoamyl alcohol. The resulting 3 [1 carbethoxyisoamyl)carbamyl] 1 methylquinolinium iodide melts at 130132 C. The calculated N content for C19H25IN2O5 is 6.1; that found is 6.0.

Example XVII Following the procedure for the preparation of ethyl a-(3-quinolinecarboxamido)propionate as set forth in Example III, but using g. of 3-quinolinecarboxylic acid and 13.8 g. of diethyl glutamate hydrochloride results in diethyl a-(S-quinoline carboxamido) glutarate.

A solution of 8 g. of this compound and of ml. of freshly distilled methyl iodide in 250 ml. of dry benzene is allowed to stand at room temperature for three days. The benzene layer is decanted from the oily methiodide, and the latter is washed with benzene and dried at 60 C. under vacuum. The resulting product is 3- [N- 1,3-dicarbethoxyl-propyl) carbamyl] -1-methylquinolinium iodide. The calculated N content for C20Hz5IN2O5 is 5.6; that found is 5.6.

Following the above procedure but using diethyl aminomalonate, diethyl aspartate or diethyl u-aminopimelate in place of diethyl glutamate results in the corresponding 1-methyl-3-(N-dicarbethoxymethylcarbamyl) quinolinium iodide, 1 methyl 3 [N (1,2 dicarbethoxyethyl)carbamyl] quinolinium iodide and 1-methyl-3-[N- (1,5-dicarbethoxypenty1)carbamyl] quinolinium iodide, respectively.

By hydrolyzing the tertiary amine intermediates of the above products (prepared in accordance with the procedure of the first paragraph of this example) with aqueous sodium hydroxide at room temperature, the corresponding 1-methyl-3-(N-dicarboxymethylcarbamyl) quinolinium iodide, l-methyl-3-[N-(l,2-dicarboxyethyl)- carbamyllquinolinium iodide, 1-methy1-3-[N(1,3-dicarboxypropyl)carbamyl] quinolinium iodide and l-methyl- 3- [N- 1,5 -dicarboxypentyl) carbamyl] quinolinium iodide, respectively, are prepared.

Example XVIII Following the procedure of Example XVII using, however, methyl sulfate in place of methyl iodide, the corresponding 1-methyl-3- [N (1,3-dicarbethoxypropyl) carbamyl] quinolinium methosulfate melting at 107110 C., is obtained. The calculated N content for C21H28N209S is 5.8; that found is 5.7.

Example XIX Following the procedure of Example XI for the preparation of ethyl a-(3-quinolinecarboxamido) hydrocinnamate, but employing 10 g. of 3-quinoline carboxylic acid, 12.7 g. of ethyl methioninate hydrochloride and 19 g. of sodium carbonate, results in ethyl N-(3-quinolinecarbonyl) methioninate.

A solution of 8 g. of this compound and of 15 ml. of freshly distilled methyl iodide in 250 ml. of dry benzene is allowed to stand at room temperature for three days. The benzene layer is decanted from the oily methiodide, and the latter is thoroughly washed with benzene and dried at 60 C. under vacuum. The resulting product is 3-[N-(1-carbethoxy-3-methylmercapto 1 propyl) carbamyl]-l-methylquinolinium iodide. The calculated N content for C18H23IN203S is 5.9; that found is 5.5.

In the same manner, the corresponding 1-methyl-3- [N (1 carbethoxy 2 methylmercaptoethyl)carbamyl] quinolinium iodide, 1-methyl-3-[N (1 carbethoxy 4- methylmercaptobutyl)carbamyl] quinolinium iodide, 1- methyl-3-[N-(l-carbethoxy 3 methylmercaptoisobutyl) carbamyl] quinolinium iodide and 1-methyl-3-[N-(1-carbethoxy 5 methylmercaptoamyl)carbamyl]quinolinium iodide are prepared by using, in place of ethyl methioninate, ethyl a-amino-fi-methylmercaptopropionate, ethyl a-amino-6-methylmercaptovalerate, ethyl a-amino- -methylmercaptoisovalerate and ethyl a-amino e-methyl mercaptocaproate, respectively.

Considerable modification is possible in the selection of the various constituents and combinations of constituents, as well as in the particular techniques employed in preparing the compounds without departing from the scope of the invention.

I claim:

1. Quaternary quinoline carboxamide salts possessing the structural formula:

1 X- R where R is selected from the group consisting of alkyl groups containing from 1 to 4 carbon atoms, allyl, benzyl, methoxybenzyl, ethoxybenzyl, methylbenzyl and methoxymethylbenzyl groups, where R1 is selected from the group consisting of alkyl groups containing from 1 to 3 carbon atoms and an A-Y group where A is selected from the group consisting of alkylene groups containing from 1 to carbon atoms, mercaptoalkylene groups, the alkylene group of which contains from 1 to 3 carbon atoms, methylmercaptoalkylene groups, the alkylene group of which contains from 1 to 3 carbon atoms, carboxyalkylene groups, the alkylene group of which contains from 2 to 3 carbon atoms, carbethoxyalkylene groups, the alkylene group of which contains from 2 to 3 carbon atoms, a phenylene group, and a phenyl alkylene group, the alkylene group of which contains from 1 to 3 carbon atoms; and where Y is selected from the group consisting of CN, COOH, CONHz and COORz, Rz being an alkyl group containing from 1 to 4 carbon atoms; and where X denotes an acid anion.

2. The compounds of claim 1 wherein R is an alkyl group containing from 1 to 4 carbon atoms, and where R1 is the group A--Y where A is an alkylene group and Y is COORz.

3. A l-methyl 3 [N-(l-carbethoxyethyl)carbamyl]- quinolinium salt.

4. 1 methyl 3 [N-(l carbethoxyethyl) carbamyl] quinolinium iodide.

5. A 1 methyl 3 (N car-bethoxymethylcarbamyl) quinolinium salt.

6. 1 methyl 3 (N carbethoxymethylcarbamyl) quinolinium iodide.

7. A 1 methyl 3 (N-p carbethoxyphenylcarbamyl) quinolinium salt.

8. 1 methyl 3 (N p-carbethoxyphenylcarbamyl) quinolinium iodide.

9. A 1 methyl 3 [N-(l cyanoethyDcarbamyl] quinolinium salt.

10. 1 methyl 3 [N (1 cyanoethyDcarbamyl] quinolinium iodide.

11. A 1 methyl 3 [N (1 car-boxamidoethyD- carbamyl] quinolinium salt.

12. l methyl 3 [N-(l carboxamidoethyDcarbamyl] quinolinium iodide.

References Cited in the file of this patent Nador: Nature, vol. 171, pp. 788-9 (1953).

Decker et al.: I. Prakt Chem. N. F., vol. 79, pp. 339-351.

Meyer et a1.: Biochem. Z., vol. 229, pp. 154-63 (1930), as abstracted in Chem. Abstn, vol. 25, pp. 2999.

UNITED STATES PATENT OFFICE Certificate of Correction Patent No. 2,798,070 July 2, 1957 Cornelius K. Cain It is hereby certified that error appears in the printed sPecification of the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 4, line 23, after 3.7 insert -g.; column 6 line 72, for 110 read 10 g.-; column 7 line 36, for 36-64 milligrams read 3264= mi igramsline 59, for 3- l-carhethoxyisoam lgcarbamyl] -1-methylread 3-[N- l-carbethoxyisoamy )carbamyl] -1-met y Signed and sealed this 24th day of September 1957.

[SEAL] Attest KARL H. AXLINE, ROBERT C. WATSON, Atteeti/ng Oflicer. Uommz'ssz'oner of Patents. 

1. QUATERNARY QUINOLINE CARBOXAMIDE SALT POSSESSING THE STRUCTURAL FORMULA: 